The relationship between blood pressure (BP) and kidney function among individuals with chronic kidney disease (CKD) remains controversial. This study evaluated the association between BP and estimated glomerular filtration rate (eGFR) decline among adults with nondiabetic stage 3 CKD. The Multi-Ethnic Study of Atherosclerosis participants with an eGFR 30–59 ml min–1 per 1.73 m2 at baseline without diabetes were included. Participants were followed over a 5-year period. Kidney function change was determined by annualizing the change in eGFR using cystatin C, creatinine and a combined equation. Risk factors for progression of CKD (defined as a decrease in annualized eGFR >2.5 ml min–1 per 1.73 m2) were identified using univariate analyses and sequential logistic regression models. There were 220 participants with stage 3 CKD at baseline using cystatin C, 483 participants using creatinine and 381 participants using the combined equation. The median (interquartile range) age of the sample was 74 (68–79) years. The incidence of progression of CKD was 16.8% using cystatin C and 8.9% using creatinine (P = 0.002). Systolic BP >140 mm Hg or diastolic BP >90 mm Hg was significantly associated with progression using a cystatin C-based (odds ratio (OR), 2.49; 95% confidence interval (CI), 1.12–5.52) or the combined equation (OR, 2.07; 95% CI, 1.16–3.69), but not when using creatinine after adjustment for covariates. In conclusion, with the inclusion of cystatin C in the eGFR assessment hypertension was an important predictor of CKD progression in a multi-ethnic cohort with stage 3 CKD.
blood pressure; glomerular filtration rate; renal disease; cystatin C; creatinine; ethnicity
To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days following hospital discharge. The study encompassed 556,090 adult members of Kaiser Permanente of Northern California hospitalized over an 8 year period, who had pre-admission estimated glomerular filtration rates (eGFR) equivalent to or greater than 45 ml/min/1.73 m2 and who survived hospitalization. After controlling for potential confounders such as baseline level of eGFR and diabetes status, dialysis-requiring ARF was independently associated with a 28-fold increase in the risk of developing stage 4 or 5 CKD and more than a twofold increased risk of death. Our study shows that in a large, community-based cohort of patients with pre-existing normal or near normal kidney function, an episode of dialysis-requiring ARF was a strong independent risk factor for a long-term risk of progressive CKD and mortality.
acute kidney injury; end-stage renal disease; epidemiology
Connective tissue growth factor (CTGF) is involved in the development and progression of kidney diseases including diabetic nephropathy and kidney fibrosis, but may also play a role in mesangial repair following injury. It is unknown whether, in the general population, urinary CTGF levels are associated with reduction of estimated glomerular filtration rate (eGFR) to less than 60 ml/min/1.73m2 (ie, development of chronic kidney disease [CKD] stage 3).
Setting & Participants
100 cases of incident CKD stage 3 and 100 age-and sex-matched controls in the Framingham Heart Study (FHS); 141 cases and 135 age-, sexand race-matched controls in the Atherosclerosis Risk in Communities (ARIC) Study. Controls had eGFR ≥60 ml/min/1.73m2 at follow-up in both studies.
Urinary CTGF concentrations.
Incident CKD stage 3, defined as eGFR <60 ml/min/1.73m2.
Stored urine samples from Framingham Heart Study and ARIC were measured for CTGF. Covariates were obtained from Framingham Heart Study and ARIC participant examinations.
In Framingham Heart Study, the median baseline urinary CTGF concentration was lower among cases (1.35 ng/mL) than controls (2.35 ng/mL; paired t-test P<0.0001). The multivariable-adjusted OR for incident CKD stage 3 was 0.33 (95% confidence interval [CI] 0.17–0.64; P<0.001) per 1-standard deviation increase in log urinary CTGF after adjustment for CKD risk factors, baseline eGFR and baseline log urinary albumin-creatinine ratio, with similar results among participants without diabetes (n=184). Results were not materially different when urinary CTGF was indexed to urinary creatinine (multivariable-adjusted OR, 0.34; 95% CI, 0.21–0.56; P<0.001). A similar, but non-significant, trend of risk of incident CKD stage 3 with lower baseline urinary CTGF concentration was observed in an independent case-control study conducted in the ARIC Study, with the strongest results observed among participants free of diabetes. This inverse relationship was robust in meta-analysis of both the overall and diabetes-free groups.
Observational study; causality cannot be inferred.
Lower urinary CTGF concentrations precede the onset of CKD stage 3 in the general population. Further work is required to fully characterize how CTGF influences risk of CKD.
To examine, the predictors of incident chronic kidney disease (CKD) in a community-based cohort of Middle East population, during a mean follow-up of 9.9 years. In a sample of 3313 non-CKD Iranian adults ≥20 years the estimated glomerular filtration rate (eGFR) was calculated at baseline and at three year intervals during three consecutive phases. The eGFR <60 mL/min/1.73 m2 was defined as CKD. Multivariate Logistic regression analysis was used to determine the independent variables associated with incident CKD. The incidence density rates of CKD were 285.3 and 132.6 per 10,000 person-year, among women and men, respectively. Female gender per se was associated with higher risk of CKD, compared with males. Among women, age, eGFR, known diabetes, being single or divorced/widowed, hypertension (marginally significant) and current smoking were independent risk factors for CKD; however the intermediate degree of education and family history of diabetes decreased the risk by 40% (P<0.05). Among male subjects, independent predictors of developing CKD included aging and hypertension (with significantly higher risk than in women, P for interaction<0.05), eGFR, new diagnosed diabetes, high normal blood pressure; abdominal obesity decreased the risk of CKD about 30% which was marginally significant. In the Iranian population,>2% of individuals develops CKD each year. Our findings confirmed that sex- specific risk predictors should be considered in primary prevention for incident CKD.
Advanced glycation end products (AGEs) are bioactive molecules found in greater concentrations in foods that have been processed at high temperatures. AGEs have been associated with impaired renal function in diabetes and in uremia. The relationship between AGEs and renal function in community-dwelling adults has not been well characterized.
Aim of the Study
The objective was to determine whether plasma AGEs are independently associated with chronic kidney disease (CKD) and predictive of renal function in older adults.
The relationship between plasma carboxymethyl-lysine (CML), an AGE, and CKD (≥stage 3 of National Kidney Foundation classification; estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) and eGFR at 3- and 6-years follow-up was examined in a population-based study of aging, the InCHIANTI study, in Tuscany, Italy.
Of 1,008 adults, aged ≥65 years, 153 (15.2%) had CKD at enrollment. Mean (Standard Deviation [S.D.]) plasma CML was 365 (110) ng/mL. Plasma CML was associated with CKD (Odds Ratio [O.R.] expressed per 1 S.D., 1.53, 95% Confidence Interval [C.I.] 1.27-1.84, P <0.0001) in a multivariate logistic regression model, adjusting for potential confounders. Plasma CML was associated with eGFR (beta = -2.77, standard error [S.E.] = 0.51, P <0.0001) at baseline, 3-year (beta = -2.54, S.E. = 0.61, P <0.0001) and 6-year follow-up visits (beta = -1.21, S.E. = 0.70, P = 0.08) in multivariate linear regression models, adjusting for potential confounders. The associations between plasma CML and prevalent CKD, eGFR, and eGFR at 3- and 6-year follow-up were significant and nearly unchanged after exclusion of adults with diabetes.
Plasma CML is independently associated with CKD and is an independent predictor of decline in renal function in older community-dwelling adults.
advanced glycation end products; aging; carboxymethyl-lysine; chronic kidney disease; renal function
Whether automated estimated glomerular filtration rate (eGFR) reporting for patients is associated with improved provider recognition of chronic kidney disease (CKD), as measured by diagnostic coding of CKD in those with laboratory evidence of the disease, has not been explored in a poor, ethnically diverse, high-risk urban patient population. A retrospective cohort of 237 adult patients (≥20 years) with incident CKD (≥1 eGFR ≥60 ml/min/1.73 m2, followed by ≥2 eGFRs <60 ml/min/1.73 m2 ≥3 months apart)—pre- or postautomated eGFR reporting—was identified within the San Francisco Department of Public Health Community Health Network (January 2005–July 2009). Patients were considered coded if any ICD-9-CM diagnostic codes for CKD (585.x), other kidney disease (580.x–581.x, 586.x), or diabetes (250.4) or hypertension (403.x, 404.x) CKD were present in the medical record within 6 months of incident CKD. Multivariable logistic regression was used to obtain adjusted odds ratios (ORs) for CKD coding. We found that, pre-eGFR reporting, 42.5 % of incident CKD patients were coded for CKD. Female gender, increased age, and non-Black race were associated with lower serum creatinine and lower prevalence of coding but comparable eGFR. Prevalence of coding was not statistically significantly higher overall (49.6 %, P = 0.27) or in subgroups after the institution of automated eGFR reporting. However, gaps in coding by age and gender were narrowed post-eGFR, even after adjustment for sociodemographic and clinical characteristics: 47.9 % of those <65 and 30.3 % of those ≥65 were coded pre-eGFR, compared to 49.0 % and 52.0 % post-eGFR (OR = 0.43 and 1.16); similarly, 53.2 % of males and 25.4 % of females were coded pre-eGFR compared to 52.8 % and 44.0 % post-eGFR (OR 0.28 vs. 0.64). Blacks were more likely to be coded in the post-eGFR period: OR = 1.08 and 1.43 (Pinteraction > 0.05). Automated eGFR reporting may help improve CKD recognition, but it is not sufficient to resolve underidentification of CKD by safety net providers.
Chronic kidney disease; Diagnostic coding; Estimated glomerular filtration rate; Female; African American
To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF).
Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF.
Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181).
A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF.
Heart failure; Myocardial infarction; Kidney disease
AIM: To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF).
METHODS: Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF.
RESULTS: Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181).
CONCLUSION: A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF.
Heart failure; Myocardial infarction; Kidney disease
The aim of this study was to determine the decline in the estimated glomerular filtration rate (eGFR) in elderly persons and to compare estimates based on creatinine and cystatin C.
In the Cardiovascular Health Study, GFR changes in an elderly cohort were estimated from serum creatinine and cystatin C measured at baseline, year 3 and year 7 in 4,380 participants (age 72 ± 5 years at entry). Outcomes were mean eGFR decline, incident chronic kidney disease (CKD) and rapid decline in eGFR (annual loss >3 ml/min/1.73 m2).
Mean annual eGFR loss as estimated from creatinine was 0.4 ± 3.6 ml/min/1.73 m2, with 16% of the participants experiencing a rapid decline. Mean eGFR loss as estimated from cystatin C was 1.8 ± 2.6, with 25% of the participants experiencing a rapid decline (p < 0.001 for both). Among participants without baseline CKD, incident CKD was detected at year 7 in 10% (n = 263) using creatinine and 19% (n = 544) using cystatin C (p < 0.001). Increasing age was the strongest predictor of rapid decline; adjusted odds ratios were 1.38 (1.16–1.65), 1.62 (1.31–1.99) and 2.96 (2.28–3.84) for participants aged 70–74, 75–79 and 80+ at baseline, compared with those aged 65–69.
In elderly persons, cystatin C estimated substantially larger declines in kidney function than creatinine did. Defining the optimal measurement of kidney function in elderly persons should be a high priority for future research.
Glomerular filtration rate; Creatinine; Cystatin C; Chronic kidney disease
Low 25-hydroxy vitamin D (25(OH)D) levels have been associated with an increased risk of albuminuria, however an association with glomerular filtration rate (GFR) is not clear. We explored the relationship between 25(OH)D levels and prevalent chronic kidney disease (CKD), albuminuria and impaired GFR, in a national, population-based cohort of Australian adults (AusDiab Study).
10,732 adults ≥25 years of age participating in the baseline survey of the AusDiab study (1999–2000) were included. The GFR was estimated using an enzymatic creatinine assay and the CKD-EPI equation, with CKD defined as eGFR <60 ml/min/1.73 m2. Albuminuria was defined as a spot urine albumin to creatinine ratio (ACR) of ≥2.5 mg/mmol for men and ≥3.5 for women. Serum 25(OH)D levels of <50 nmol/L were considered vitamin D deficient. The associations between 25(OH)D level, albuminuria and impaired eGFR were estimated using multivariate regression models.
30.7% of the study population had a 25(OH)D level <50 nmol/L (95% CI 25.6-35.8). 25(OH)D deficiency was significantly associated with an impaired eGFR in the univariate model (OR 1.52, 95% CI 1.07-2.17), but not in the multivariate model (OR 0.95, 95% CI 0.67-1.35). 25(OH)D deficiency was significantly associated with albuminuria in the univariate (OR 2.05, 95% CI 1.58-2.67) and multivariate models (OR 1.54, 95% CI 1.14-2.07).
Vitamin D deficiency is common in this population, and 25(OH)D levels of <50 nmol/L were independently associated with albuminuria, but not with impaired eGFR. These associations warrant further exploration in prospective and interventional studies.
Albuminuria; Chronic kidney disease; Glomerular filtration rate; and Vitamin D
Recent studies have suggested an association between hyperuricemia and adverse renal outcomes in nondiabetic populations. Data on the relationship between hyperuricemia and the risk of incident chronic kidney disease (CKD) in type 2 diabetic patients with normal or near-normal kidney function are lacking. We determined whether baseline serum uric acid levels predict the subsequent development of CKD in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS
We followed 1,449 type 2 diabetic patients with normal kidney function and without overt proteinuria for 5 years for the occurrence of incident CKD (defined as overt proteinuria or estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2).
During a 5-year follow-up period, 194 (13.4%) patients developed incident CKD. The cumulative incidence of CKD was significantly greater in patients with hyperuricemia than in those without hyperuricemia (29.5 vs. 11.4%, P < 0.001). In univariate logistic regression analysis, the presence of hyperuricemia roughly doubled the risk of developing CKD (odds ratio [OR] 2.55 [95% CI 1.71–3.85], P < 0.001). After adjusting for age, sex, BMI, smoking status, diabetes duration, systolic blood pressure, antihypertensive treatment, insulin therapy, HbA1c, eGFR, and albuminuria, hyperuricemia was associated with an increased risk of incident CKD (adjusted OR 2.10 [1.16–3.76], P < 0.01). In continuous analyses, a 1-SD increment in the serum uric acid level was significantly associated with a 21% increased risk of CKD.
In type 2 diabetic individuals with preserved kidney function, hyperuricemia seems to be an independent risk factor for the development of incident CKD.
Proteinuric diabetic patients with reduced glomerular filtration rate (GFR) are at high risk of renal and cardiovascular disease progression and treatment-related adverse events. This post hoc analysis assessed the efficacy and safety of aliskiren added to the maximal recommended dose of losartan according to baseline estimated GFR (eGFR) (stage 1–3 chronic kidney disease [CKD]).
RESEARCH DESIGN AND METHODS
In the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study, 599 hypertensive patients with type 2 diabetes and nephropathy received 6 months of aliskiren (150 mg daily titrated to 300 mg daily after 3 months) or placebo added to 100 mg losartan and optimal antihypertensive therapy. Exclusion criteria included eGFR <30 ml/min per 1.73 m2 and serum potassium >5.1 mmol/l.
Baseline characteristics were similar between treatment groups in all CKD stages. The antiproteinuric effects of aliskiren were consistent across CKD stages (19, 22, and 18% reduction). In the stage 3 CKD group, baseline serum creatinine levels were equal, but renal dysfunction, prespecified as a postrandomization serum creatinine elevation >176.8 μmol/l (2.0 mg/dl) occurred more frequently in the placebo group (29.2 vs. 13.6%, P = 0.032). Serum potassium elevations >5.5 mmol/l (based on a single measurement) were more frequent with aliskiren (22.5 vs. 13.6%) in stage 3 CKD. Adverse event rates were similar between treatments, irrespective of CKD stage.
Aliskiren added to losartan reduced albuminuria and renal dysfunction and was well tolerated, except for hyperkalemia (stage 3), independent of baseline CKD stage in patients with type 2 diabetes, hypertension, and nephropathy.
The relations between chronic kidney disease (CKD) and incident heart failure remain unclear.
Methods and Results
We related CKD to incident nonfatal heart failure and cardiovascular (CVD) death (as separate and combined endpoints) in 10,181 male participants (mean age, 67years). Kidney function was assessed by estimated glomerular filtration rate (eGFR) using Modification of Diet in Renal Disease equation in clinically relevant categories of <60 and ≥60 ml/min/1.73 m2 (referent); and <45, 45 to 60, 60 to 90 and ≥90 ml/min/1.73 m2 (referent). During follow up (mean 10.1years; range 0.03-12.2), 439 developed heart failure and 832 had CVD death/heart failure. In multivariable models, men with eGFR <60ml/min/1.73 m2 had a 2-fold risk of heart failure (95% confidence interval [CI], 1.62-2.56, p<0.0001) compared to referent category. The hazard ratio [HR] (with corresponding 95% CI) for development of heart failure according to eGFR categories of 60-90, 45-60, and <45ml/min/1.73m2 compared to referent category were 1.24 (0.98-1.56), 2.58 (1.91-3.49) and 1.52 (0.92-2.76) respectively. In the analyses restricted to subgroup of non-diabetics and normotensive individuals at baseline (n=7545), men with eGFR <60 ml/min/1.73 m2 had 2.2-fold risk of heart failure (95% CI 1.66-2.95), compared to men with eGFR≥60 ml/min/1.73 m2. Additionally, risk of heart failure or CVD death was >2.5-fold higher among individuals with eGFR 45-60 and <45 ml/min/1.73 m2, compared to referent category.
Moderate level of CKD, even in absence of diabetes and hypertension at baseline, is associated with a higher risk of developing heart failure and CVD death/heart failure in men.
Heart Failure; Congestive; Epidemiology; Renal disease
Metabolic acidosis is known to accelerate the progression of chronic kidney disease (CKD). However, whether undetermined anions as indicated by the adjusted anion gap (aAG) are associated with estimated glomerular filtration rate (eGFR) decline in patients with CKD is unclear.
Data from 42 patients with CKD (baseline eGFR, 7.1-52.0 ml/min/ 1.73 m2) without massive proteinuria (urinary protein-creatinine ratio, UPCR <3.5) were retrospectively analyzed. aAG was calculated from serum sodium, serum chloride, serum bicarbonate, serum albumin, serum potassium, serum calcium and serum phosphate. The association between the percentage of the 6-month change of eGFR (%ΔeGFR/6m) and aAG was examined.
The mean baseline eGFR was 27.5 ± 11.1 ml/min/1.73 m2 and the mean %ΔeGFR/6m was 13.8 ± 10.3. UPCR and aAG were 1.13 ± 0.93 and 9.48 ± 1.88, respectively. %ΔeGFR/6m was associated with aAG (r = 0.438, p < 0.005), but not with UPCR (r = 0.194, p = 0.218). In multivariate linear regression analyses, aAG remained significantly associated with %ΔeGFR/6m (β = 0.45, p < 0.01) after controlling for age, baseline eGFR, UPCR and HCO3- concentration.
These data suggest that aAG appears to be associated with the progression of CKD. aAG might be an independent predictor of CKD progression.
Chronic kidney disease; Glomerular filtration rate decline; Adjusted anion gap
Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD), although shared risk factors may mediate much of the association. We related CKD and CVD in the setting of specific CVD risk factors and determined whether more advanced CKD was a CVD risk equivalent. The Framingham Heart Study original cohort (n=2471, mean age 68 years, 58.9% women) was studied. Glomerular filtration rate (eGFR) was estimated using the simplified Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR < 59 mL/min per 1.73 m2 (women) and < 64 (men) and Stage 3b CKD defined as eGFR 30-44 (women) and 30-50 (men). Cox Proportional Hazard models adjusting for CVD risk factors were used to relate CKD to CVD. We tested for effect modification by CVD risk factors. Overall, 23.2% of the study sample had CKD (n=574; mean eGFR 50 mL/min per 1.73 m2) and 5.3% had Stage 3b CKD (n=131; mean eGFR 42 mL/min per 1.73 m2). In multivariable models (mean follow-up time 16 years), Stage 3 CKD was marginally associated with CVD (HR=1.17, 95% CI 0.99-1.38, p=0.06), whereas Stage 3b CKD was associated with CVD [HR=1.41, 95% CI 1.05-1.91, p=0.02]. Upon testing CVD risk equivalency, the risk of CVD for Stage 3b CKD among participants with prior CVD was significantly lower as compared to participants with prior CVD and no Stage 3b CKD (age- and sex-adjusted HR for CVD = 0.66 [95% CI 0.47 to 0.91], p=0.01). Low HDL modified the association between CKD and CVD (p-value=0.004 for interaction). Stage 3b CKD is associated with CVD but is not a CVD risk equivalent. In conclusion, CVD risk in the setting of CKD is higher in the setting of low HDL cholesterol.
American Indians and Alaska Natives (AIAN) have a high incidence of end-stage renal disease. Less is known about chronic kidney disease (CKD) among AIAN and whether risk factors differ for low estimated glomerular filtration rate (eGFR) versus albuminuria with a normal eGFR.
Cross-sectional study examining the associations of age, sex, smoking, obesity, diabetes, hypertension, family history, and geographic region with CKD among a screened population of AIAN participants in the Kidney Early Evaluation Program from 2000 to 2006. CKD was defined by the presence of either a low eGFR, <60 ml/min/1.73 m2, or albuminuria, a urine albumin/creatinine ratio ≥30 mg/g.
The prevalence of any CKD was 29%, of low eGFR was 17%, and of albuminuria with a normal eGFR was 12%. Older age was the strongest predictor of low eGFR (61+ years OR 8.42, 95% CI 5.92–11.98), followed by hypertension (OR 2.38, 95% CI 1.74–3.26). In contrast, diabetes (OR 2.04, 95% CI 1.57–2.64) and hypertension (OR 2.63, 95% CI 1.93–3.59) were the only predictors of albuminuria among persons with a normal eGFR.
The burden of CKD was high among this screened population of AIAN, and different risk factor patterns were associated with low eGFR and albuminuria. Innovative programs and longitudinal research are needed to address CKD among AIAN.
Chronic kidney disease; Risk factors; American Indians; Alaska Natives
Objective: In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD).
Method: Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m2, eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m2 (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events.
Results: baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03)
Conclusions: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.
arterial stiffness; cardiovascular disease; chronic kidney disease; pulse wave velocity.
To assess the cardiovascular risk of diabetic subjects with chronic kidney disease (CKD) based on different estimated glomerular filtration rate (eGFR) equations and to evaluate which definition of CKD best improves cardiovascular risk prediction of the Framingham Cardiovascular Risk Score (Framingham-CV-RS).
RESEARCH DESIGN AND METHODS
CKD was defined as eGFR <60 mL/min/1.73 m2, estimated by the creatinine-based Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and a cystatin C–based equation (CKD-CysC). Cox regression was used to estimate hazard ratios (HRs) of subjects with CKD for incident cardiovascular events in a cohort of 1,153 individuals with diabetes (baseline age 50–74 years). Furthermore, the CKD definitions were added individually to a reference model comprising the Framingham-CV-RS variables and HbA1c, and measures of model discrimination and reclassification were assessed.
During 5 years of follow-up, 95 individuals had a primary cardiovascular event. Crude HRs were increased for all CKD definitions. However, after adjusting for established cardiovascular risk factors, HRs for both creatinine-based CKD definitions were attenuated to point estimates of 1.03, whereas the HRs for the cystatin C–based CKD definition remained significantly increased (HR 1.75 [95% CI 1.07–2.87]). Extension of the reference model by the different CKD definitions resulted in an increase in the c statistic only when adding CKD-CysC (from 0.638 to 0.644) along with a net reclassification improvement of 8.9%.
Only the cystatin C–based CKD definition was an independent risk predictor for cardiovascular events in our diabetic study cohort and indicated a potentially better clinical utility for cardiovascular risk prediction than creatinine-based equations.
Serum creatinine is commonly used to diagnose chronic kidney disease (CKD), but may underestimate CKD in older adults when compared with using glomerular filtration rates (eGFR). The magnitude of this underestimation is not clearly defined.
Using the Modification of Diet in Renal Disease (MDRD) equation, to describe both the prevalence and the magnitude of underestimation of stage 3 CKD (GFR 30–59 ml/min/1.73 m2), as well as ideal serum creatinine cutoff values to diagnose stage 3 CKD among Americans ≥65 years of age.
A total of 3,406 participants ≥65 years of age from the 1999–2004 National Health and Nutrition Examination Surveys (NHANES).
Serum creatinine levels were used to determine eGFR from the MDRD equation. Information on clinical conditions was self-reported.
Overall, 36.1% of older adults in the US have stage 3 or greater CKD as defined by eGFR values. Among older adults with stage 3 CKD, 80.6% had creatinine values ≤1.5 mg/dl, and 38.6% had creatinine values ≤1.2 mg/dl. Optimal cutoff values for serum creatinine in the diagnosis of stage 3 CKD in older adults were ≥1.3 mg/dl for men and ≥1.0 mg/dl for women, regardless of the presence or absence of hypertension, diabetes, or congestive heart failure.
Use of serum creatinine underestimates the presence of advanced (stage 3 or greater) CKD among older adults in the US. Automated eGFR reporting may improve the accuracy of risk stratification for older adults with CKD.
chronic kidney disease; serum creatinine; older adults; glomerular filtration rate
Studies have documented an association between chronic kidney disease (CKD) and increased risk of end-stage renal disease (ESRD), death and comorbidities, including cardiovascular disease and metabolic syndrome, in the general population. However, there is little data on the relationship between CKD and ADE (AIDS defining event), and to our knowledge, no studies have analyzed death as a competing risk for ADE among HIV-infected persons. An observational cohort study was performed to determine the incidence and risks for developing an ADE or death among HIV-infected persons with and without CKD from 1998 – 2005. CKD was defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 using the CKD-Epidemiology Collaboration (CKD-EPI) equation. Log rank test and Cox regression which determined time to development of ADE and/or death as combined and separate outcomes, and competing risk models for ADE versus mortality, were performed. Among the 2,127 persons that contributed to the 5,824 person years of follow-up: 22% were female, 34% African-American, 38% on HAART, and 3% had CKD at baseline. ADE occurred in 227 (11%) persons and there were 80 (4%) deaths. CKD was not significantly associated with ADE/death (HR 1.3, 95% CIs: 0.5, 3.2), ADE (HR 1.0, 95% CIs: 0.4, 3.1), or death (HR 1.6, 95% CIs: 0.4, 3.1). Competing risk analyses confirmed no statistically significant associations between CKD and these outcomes. CKD was uncommon in HIV-infected persons presenting for care in this racially diverse cohort, and was not independently associated with risk of developing an ADE or dying during follow-up.
HIV; CKD; AIDS defining event (ADE); mortality
The short-term effects of multifactorial intervention for cardiovascular disease (CVD) prevention on renal function and serum uric acid (SUA) levels in patients with stage 3 chronic kidney disease (CKD) and multiple CVD risk factors are unclear. The aim of the study was to prospectively assess these effects.
Material and methods
This post hoc analysis of 5 "best practice" studies involved patients with multiple CVD risk factors. Estimated glomerular filtration rate (eGFR) was assessed using the Modification of Diet in Renal Disease (MDRD) formula. Among the 4,153 patients, 1,235 (29.7%) had stage 3 CKD (eGFR between 30 and 59 ml/min/1.73 m2). A baseline visit was followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimize drug treatment, including a statin, for all vascular risk factors. After 6 months eGFR and SUA levels were re-evaluated.
The intervention improved compliance to lifestyle measures and increased the use of evidence-based medication, including a statin. There was also a 5.6% increase in eGFR (p < 0.001) in patients with stage 3 CKD and a 6.1% reduction in SUA levels (p < 0.001). Among patients with stage 3 CKD, 127 (10.3%) improved to stage 2 CKD and 9 (0.7%) advanced to stage 4 CKD by the end of the 6-month study period. There were no major side-effects.
Multitargeted intervention, including a statin, may improve renal function and reduce SUA levels within 6 months, thus offsetting 2 potential CVD risk factors in high-risk patients.
renal function; uric acid; dyslipidaemia; diabetes mellitus; hypertension; metabolic syndrome; multifactorial intervention; statin
Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV) co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR <60 mL/min/1.73 m2 or 25% decline with a baseline <60). Generalized Estimating Equations were used to model the odds of progressive CKD. At baseline, 13.8% and 3.3% of participants were co-infected with HCV and HBV, respectively. Median eGFR was 111, and 3.7% developed progressive CKD. After adjustment, the odds of progressive CKD were increased in participants with HCV (OR 1.72, 95% CI 1.07–2.76) or HBV (OR 2.26, 95% CI 1.15–4.44). Participants with undetectable or low HCV-RNA had similar odds of progressive CKD as HCV seronegative participants, while participants with HCV-RNA >800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60–5.90). Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia and CKD.
ClinicalTrials.gov NCT00027352; NCT00004978
Novel biomarkers may improve our ability to predict which patients with chronic kidney disease (CKD) are at higher risk for progressive loss of renal function. Here we assessed the performance of urine neutrophil gelatinase-associated lipocalin (NGAL) for outcome prediction in a diverse cohort of 3386 patients with CKD in the CRIC study. In this cohort, the baseline mean estimated glomerular filtration rate (eGFR) was 42.4 ml/min/1.73m2; the median 24-hour urine protein was 0.2 gm/day; and the median urine NGAL concentration was 17.2 ng/mL. Over an average follow-up of 3.2 years, there were 689 cases in which the eGFR was decreased by half or incident end-stage renal disease developed. Even after accounting for eGFR, proteinuria and other known CKD progression risk factors, urine NGAL remained a significant independent risk factor (Cox model hazard ratio 1.70 highest to lowest quartile). The association between baseline urine NGAL levels and risk of CKD progression was strongest in the first two years of biomarker measurement. Within this time frame, adding urine NGAL to a model which included eGFR, proteinuria and other CKD progression risk factors led to net reclassification improvement of 24.7%; but the C-statistic remained nearly identical. Thus, while urine NGAL was an independent risk factor of progression among patients with established CKD of diverse etiology, it did not substantially improve prediction of outcome events.
Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD.
Methods and Results
We studied adults with CKD (defined as persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002–2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206,229 adults with CKD, 16,463 developed incident AF. During a mean follow-up of 5.1± 2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) compared with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in rate of ESRD (hazard ratio 1.67, 95% confidence interval: 1.46–1.91).
Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD.
arrhythmia; fibrillation; kidney
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
Chronic kidney disease (CKD) affects about 6%–11% of the general population, and progression to end stage renal disease (ESRD) has a significant public health impact. Family studies suggest that the risk for CKD and ESRD is heritable. Unraveling the genetic underpinning of risk for these diseases may lead to the identification of novel mechanisms and thus diagnostic and therapeutic tools. We have previously identified 16 genetic markers in association with kidney function and prevalent CKD in general population studies. However, little is known about the relevance of these SNPs to the initial development of CKD or to ESRD risk. Therefore, we have now analyzed the association of these markers with the initiation of CKD in more than 26,000 individuals from the general population using serial estimations of kidney function, and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). We show that many of the 16 markers are also associated or show a strong trend towards association with initiation of CKD, while only 2 markers are nominally associated with ESRD. Further work is required to characterize the association of genetic determinants of different stages of CKD progression.